Functional enhancement of beta cells in transplanted pancreatic islets by secretion signal peptide-linked exendin-4 gene transduction

Title
Functional enhancement of beta cells in transplanted pancreatic islets by secretion signal peptide-linked exendin-4 gene transduction
Author(s)
정지헌육심명[육심명]정윤석[정윤석]임복현[임복현]이민형[이민형]안철희[안철희]이동윤[이동윤]변영로[변영로]
Keywords
EXENATIDE EXENDIN-4; PORCINE ISLETS; DIABETIC RATS; APOPTOSIS; MICE; XENOTRANSPLANTATION; ACTIVATION; THERAPY
Issue Date
201205
Publisher
ELSEVIER SCIENCE BV
Citation
JOURNAL OF CONTROLLED RELEASE, v.159, no.3, pp.368 - 375
Abstract
This study assessed whether the newly designed exendin-4 (Ex-4) gene with highly releasable characteristics could enhance the beta cell function, thereby attenuating the essential islet mass required to cure diabetes. We constructed a lentivirus system encoding for a highly releasable secretion signal peptide, the peptide linked Ex-4 (SP-Ex-4) gene. After the transduction of lentivirus encoding for SP-Ex-4 (LV-SP-Ex-4) gene into the islets, the therapeutic effects of Ex-4 secreted were evaluated by conducting glucose-stimulated insulin secretion and cytokine-or hypoxia-induced apoptosis. Additionally, the effect of reduced islet numbers for transplantation was evaluated via in vivo models. The transduction of LV-SP-Ex-4 gene did not affect the viability of islets. In diabetic animal models, 50 islets expressing Ex-4 were transplanted to cure the diabetic nude mice, whereas at least 150 untransduced islets had to be transplanted to cure the diabetic nude mice. When the transduced islets were transplanted into diabetic immunocompetent mice, the survival rate of the mice was 18.0 +/- 4.9 days; however, when the untransduced islets were transplanted, they were rejected within 10.0 +/- 0.6 days. Therefore, the highly releasable Ex-4 could enhance the beta cell function with slightly enhanced viability of transplanted islets, presenting as a potential technology for overcoming islet shortage. (C) 2012 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/28297http://dx.doi.org/10.1016/j.jconrel.2012.01.029
ISSN
0168-3659
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약학대학 > 약학부 > Articles
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